In Vitro 3D Spheroid Culture System Displays Sustained T Cell-dependent CLL Proliferation and Survival.

Chronic lymphocytic leukemia (CLL) cells are highly dependent on microenvironmental cells and signals. The lymph node (LN) is the critical site of in vivo CLL proliferation and development of resistance to both chemotherapy and targeted agents. We present a new model that incorporates key aspects of the CLL LN, which enables investigation of CLL cells in the context of a protective niche.

Ibrutinib sensitizes CLL cells to venetoclax by interrupting TLR9-induced CD40 upregulation and protein translation.

Chronic lymphocytic leukemia (CLL) cells upregulate Bcl-2 proteins within the lymph node (LN) microenvironment. Signaling via B-cell receptor, Toll-like receptors and CD40 collectively reduce sensitivity to the BCL-2 inhibitor venetoclax. Time-limited treatment with venetoclax plus the BTK-inhibitor ibrutinib results in deep remissions, but how this combination affects LN-related signaling is not yet completely clear.

Untargeted Metabolomics Identifies Potential Hypertrophic Cardiomyopathy Biomarkers in Carriers of Founder Variants.

Hypertrophic cardiomyopathy (HCM) is the most prevalent monogenic heart disease, commonly caused by pathogenic variants, and a significant cause of sudden cardiac death. Severity is highly variable, with incomplete penetrance among genotype-positive family members. Previous studies demonstrated metabolic changes in HCM.

Distinct Metabolomic Signatures in Preclinical and Obstructive Hypertrophic Cardiomyopathy.

Hypertrophic Cardiomyopathy (HCM) is a common inherited heart disease with poor risk prediction due to incomplete penetrance and a lack of clear genotype-phenotype correlations. Advanced imaging techniques have shown altered myocardial energetics already in preclinical gene variant carriers. To determine whether disturbed myocardial energetics with the potential to serve as biomarkers are also reflected in the serum metabolome, we analyzed the serum metabolome of asymptomatic carriers in comparison to healthy controls and obstructive HCM patients (HOCM).

Metabolomics in Severe Aortic Stenosis Reveals Intermediates of Nitric Oxide Synthesis as Most Distinctive Markers.

Background: Calcific aortic valve disease (CAVD) is a rapidly growing global health problem with an estimated 12.6 million cases globally in 2017 and a 112% increase of deaths since 1990 due to aging and population growth. CAVD may develop into aortic stenosis (AS) by progressive narrowing of the aortic valve.

Strength of patient cohorts and biobanks for cardiomyopathy research.

In 2011 the Netherlands Heart Foundation allocated funding (CVON, Cardiovasculair Onderzoek Nederland) to stimulate collaboration between clinical and preclinical researchers on specific areas of research. One of those areas involves genetic heart diseases, which are frequently caused by pathogenic variants in genes that encode sarcomere proteins. In 2014, the DOSIS (Determinants of susceptibility in inherited cardiomyopathy: towards novel therapeutic approaches) consortium was initiated, focusing their research on secondary disease hits involved in the onset and progression of cardiomyopathies.

Correction to: Extra energy for hearts with a genetic defect: ENERGY trial.

Correction to: Neth Heart J 2019 https://doi.org/10.1007/s12471-019-1239-0 In the version of the article originally published online, there was an error in Fig.

Extra energy for hearts with a genetic defect: ENERGY trial.

Aims: Previous studies have shown that hypertrophic cardiomyopathy mutation carriers have a decreased myocardial energy efficiency, which is thought to play a key role in the pathomechanism of hypertrophic cardiomyopathy (HCM). The ENERGY trial aims to determine whether metabolic drugs correct decreased myocardial energy efficiency in HCM mutation carriers at an early disease stage.

Methods: 40 genotype-positive, phenotype-negative MYH7 mutation carriers will be treated for two months with trimetazidine or placebo in a double-blind randomised study design.

Sex differences in hypertrophic cardiomyopathy: new insights.

Purpose Of Review: Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy, diagnosed by left ventricular hypertrophy of at least 15 mm maximal wall thickness (MWT). Recent studies reported a sex difference in clinical presentation, progression and outcome of HCM. This review provides an overview of recent studies into sex differences in HCM.

[Hypertrophic cardiomyopathy].

Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease. Its prevalence is estimated between 1:500 and 1:200. HCM is defined by left ventricular hypertrophy (wall thickness ≥ 15 mm) in absence of abnormal loading conditions such as hypertension.

Synthesis and characterization of fluorinated anatase nanoparticles and subsequent N-doping for efficient visible light activated photocatalysis.

Fluorinated-titanium dioxide (TiO-F) nanoparticles in a pure anatase polymorph was precipitated from solution by hydrolysis of titanium oxychloride, using urea and ammonia as precipitation agents and potassium fluoride as a source of fluorine anion. A further wet attrition milling in presence of glycine completed by a heat treatment allowed an additional nitrogen doping of TiO (TiO-F&N-HT). The morphology and crystalline structure of the as-synthesized powder was determined by transmission electron microscopy (TEM) and X-ray diffraction (XRD) and showed that TiO powder was composed of nanoparticles with narrow size distribution which crystallized in the anatase phase.

Synergistic Effect of Fluorinated and N Doped TiO₂ Nanoparticles Leading to Different Microstructure and Enhanced Photocatalytic Bacterial Inactivation.

This work focuses on the development of a facile and scalable wet milling method followed by heat treatment to prepare fluorinated and/or N-doped TiO₂ nanopowders with improved photocatalytic properties under visible light. The structural and electronic properties of doped particles were investigated by various techniques. The successful doping of TiO₂ was confirmed by X-ray photoelectron spectroscopy (XPS), and the atoms appeared to be mainly located in interstitial positions for N whereas the fluorination is located at the TiO₂ surface.

Investigating the Photocatalytic Degradation of Oil Paint using ATR-IR and AFM-IR.

As linseed oil has a longstanding and continuing history of use as a binder in artistic paints, developing an understanding of its degradation mechanism is critical to conservation efforts. At present, little can be done to detect the early stages of oil paint deterioration due to the complex chemical composition of degrading paints. In this work, we use advanced infrared analysis techniques to investigate the UV-induced deterioration of model linseed oil paints in detail.

Determination of early warning signs for photocatalytic degradation of titanium white oil paints by means of surface analysis.

Titanium white (TiO) has been widely used as a pigment in the 20th century. However, its most photocatalytic form (anatase) can cause severe degradation of the oil paint in which it is contained. UV light initiates TiO-photocatalyzed processes in the paint film, degrading the oil binder into volatile components resulting in chalking of the paint.

Responses to Microbial Challenges by SLAMF Receptors.

The SLAMF family (SLAMF) of cell surface glycoproteins is comprised of nine glycoproteins and while SLAMF1, 3, 5, 6, 7, 8, and 9 are self-ligand receptors, SLAMF2 and SLAMF4 interact with each other. Their interactions induce signal transduction networks in trans, thereby shaping immune cell-cell communications. Collectively, these receptors modulate a wide range of functions, such as myeloid cell and lymphocyte development, and T and B cell responses to microbes and parasites.

The cell surface receptor Slamf6 modulates innate immune responses during Citrobacter rodentium-induced colitis.

The homophilic cell surface receptors CD150 (Slamf1) and CD352 (Slamf6) are known to modulate adaptive immune responses. Although the Th17 response was enhanced in Slamf6(-/-) C57BL/6 mice upon oral infection with Citrobacter rodentium, the pathologic consequences are indistinguishable from an infection of wild-type C57BL/6 mice. Using a reporter-based binding assay, we show that Slamf6 can engage structures on the outer cell membrane of several Gram(-) bacteria.

Migration of myeloid cells during inflammation is differentially regulated by the cell surface receptors Slamf1 and Slamf8.

Previous studies have demonstrated that the cell surface receptor Slamf1 (CD150) is requisite for optimal NADPH-oxidase (Nox2) dependent reactive oxygen species (ROS) production by phagocytes in response to Gram- bacteria. By contrast, Slamf8 (CD353) is a negative regulator of ROS in response to Gram+ and Gram- bacteria. Employing in vivo migration after skin sensitization, induction of peritonitis, and repopulation of the small intestine demonstrates that in vivo migration of Slamf1-/- dendritic cells and macrophages is reduced, as compared to wt mice.

Glucocorticoid-Induced TNF Receptor Family-Related Protein Ligand is Requisite for Optimal Functioning of Regulatory CD4(+) T Cells.

Glucocorticoid-induced tumor necrosis factor receptor family-related protein (TNFRSF18, CD357) is constitutively expressed on regulatory T cells (Tregs) and is inducible on effector T cells. In this report, we examine the role of glucocorticoid-induced TNF receptor family-related protein ligand (GITR-L), which is expressed by antigen presenting cells, on the development and expansion of Tregs. We found that GITR-L is dispensable for the development of naturally occurring FoxP3(+) Treg cells in the thymus.

Glucocorticoid-induced TNF receptor family-related protein ligand regulates the migration of monocytes to the inflamed intestine.

Glucocorticoid-induced TNF receptor family-related protein (GITR) regulates the function of both T cells and antigen-presenting cells (APCs), while the function of GITR ligand (GITR-L) is largely unknown. Here we evaluate the role of GITR-L, whose expression is restricted to APCs, in the development of enterocolitis. On injecting naive CD4(+) T cells, GITR-L(-/-)Rag(-/-) mice develop a markedly milder colitis than Rag(-/-) mice, which correlates with a 50% reduction of Ly6C(+)CD11b(+)MHCII(+) macrophages in the lamina propria and mesenteric lymph nodes.

Signaling lymphocyte activation molecule regulates development of colitis in mice.

Background & Aims: Signaling lymphocyte activation molecule (Slamf)1 is a co-stimulatory receptor on T cells and regulates cytokine production by macrophages and dendritic cells. Slamf1 regulates microbicidal mechanisms in macrophages, therefore we investigated whether the receptor affects development of colitis in mice.

Methods: We transferred CD45RB(hi) CD4(+) T cells into Rag(-/-) or Slamf1(-/-)Rag(-/-) mice to induce colitis.